The goal of this project is to elucidate key features of the expression and function of a new family of macrocyclic defensins termed theta -defensins expressed in primate myeloid cells. Rhesus theta defensin 1 (RTD-1) is prototype of this peptide family. The three specific aims are: 1) to characterize the constitutive and inducible expression of theta -defensin mRNAs and peptides in myeloid cells; 2) to test the hypotheses that theta -defensins are delivered to the phagosome during cellular activation and to determine the contribution of these peptides to killing within the phagolysosome; 3) to determine the molecular mechanism of theta -defensin-mediated bacterial killing. These studies should provide insights into the peptides. mechanism(s) of action, molecular basis of selectivity, and other potential interactions with host tissues or microbial structures.